Monoclonal antibodies to surface components (antigens) of cerebellar cells obtained from normal and neurologically mutant mice will be prepared by the lymphocyte hybridoma technique. Recipient mice will be sensitized to freshly prepared mixed cell populations, enriched cell fractions prepared by unit gravity sedimentation, and primary cultures of these cells derived from both normal and mutant cerebella. The monospecific antibodies will initially be used a) to identify specific cell types, b) detect differentiation antigens, and c) screen for cell surface differences between normal and mutant cells in primary cerebellar cultures using indirect immunofluorescence. Populations of well-defined, restricted cell type will then be produced using fluorescence-activated cell sorting, affinity chromatography and complement-mediated cytotoxicity techniques. Monoclonal antibodies will be tested for their effects on the in vitro developmental properties of both normal and mutant cerebellar cells in culture. Properties tested will be: morphological (neurite outgrowth, cell migration, etc.), pharmacological (receptor development, putative neurotransmitter release and uptake), and physiological (ion flux changes). The overall aim of this project is to use monoclonal antibodies to begin to identify the molecular nature and elucidate the role(s) of specific brain cell surface determinants in intercellular recognition and function.